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RAGE mRNA expression in the diabetic mouse kidney
F N Ziyadeh1, M P Cohen, J Guo
1Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Abstract:
Receptors for advanced glycation end products (RAGE), which bind and internalize AGE-modified proteins formed from oxidation and other products of the nonenzymatic glycation reaction, have been mechanistically implicated in the development of the chronic complications of diabetes. In the present experiments, we sought evidence for the participation of RAGE in diabetic nephropathy by analysis of steady state levels of mRNA encoding RAGE in the renal cortex of a well-defined animal model (the db/db mouse) that develops renal pathology similar to that found in human diabetes. In these animals, increased AGE-product formation was confirmed by measurement of fluorescence in serum and renal cortex proteins. Renal involvement was confirmed by demonstration of increased urine albumin excretion and elevated serum creatinine concentrations relative to nondiabetic (db/m) littermate controls. Despite elevated concentrations of circulating and tissue AGE-modified proteins, the level of RAGE mRNA expression in renal cortex of diabetic mice did not significantly differ from that in nondiabetic littermate controls. The findings militate against changes in RAGE expression in the pathogenesis of renal abnormalities in this animal model.
Insights
This study investigated the role of Receptors for Advanced Glycation End products (RAGE) in diabetic kidney disease. Researchers found that RAGE mRNA levels did not change in diabetic mice, suggesting it may not drive kidney complications.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Receptors for Advanced Glycation End products (RAGE) are implicated in diabetic complications.
- Advanced Glycation End products (AGEs) accumulate in diabetes, contributing to tissue damage.
- Diabetic nephropathy is a major complication of diabetes, characterized by kidney pathology.
Purpose of the Study:
- To investigate the role of RAGE in diabetic nephropathy.
- To analyze RAGE mRNA expression in the renal cortex of a diabetic mouse model.
- To determine if altered RAGE expression contributes to diabetic kidney disease pathogenesis.
Main Methods:
- Utilized the db/db mouse model, which develops diabetic renal pathology.
- Measured AGE-product formation via fluorescence in serum and renal cortex.
- Assessed renal involvement through urine albumin excretion and serum creatinine levels.
- Quantified steady-state levels of RAGE mRNA in the renal cortex.
Main Results:
- Diabetic mice exhibited increased AGE-product formation, albuminuria, and elevated serum creatinine.
- Despite increased AGEs, RAGE mRNA expression in the renal cortex was not significantly different between diabetic and control mice.
- These findings indicate no significant change in RAGE expression in this diabetic nephropathy model.
Conclusions:
- Changes in RAGE mRNA expression do not appear to be a primary driver of renal abnormalities in this diabetic mouse model.
- The study suggests that other mechanisms, rather than altered RAGE expression, may be involved in the pathogenesis of diabetic nephropathy.
- Further research is needed to fully elucidate the role of RAGE in diabetic kidney disease.